Tinnitus is a common auditory disorder that is often the result of extreme sound exposure. An estimated 5-15% of the population experiences chronic tinnitus, with many millions of those sufferers disabled by this condition. With an even higher prevalence of chronic tinnitus in recent war veterans (tinnitus is the most prevalent service-connected disability for US veterans receiving compensation, the personal and financial costs of tinnitus have expanded dramatically. Despite the high prevalence of tinnitus, the neuronal mechanisms that mediate the initiation (induction) and the maintenance (expression) of the disorder remain poorly understood. As a result, at this time there is no generally accepted treatment, cure or preventive method for tinnitus.
Not surprisingly, in light of the significance of tinnitus as a health problem, several drug trials for tinnitus therapy are in late stage development or have reached the market (Cederroth, C. R.; Canlon, B.; Langguth, B., “Hearing loss and tinnitus—are funders and industry listening?” Nature Biotechnology 2013, 31, 972-974). There is strong evidence that K-channels play a critical role in the development of tinnitus. K-channels, by decreasing the Rm of postsynaptic membranes, reduce membrane response time and shorten the duration of EPSPs and APs. This indicates that K-channels in auditory synapses are playing a critical role in improving temporal resolution of the auditory synaptic transmission (Oak, M.-H.; Yi, E., “Voltage-gated K+ channels contributing to temporal precision at the inner hair cell-auditory afferent nerve fiber synapses in the mammalian cochlea.” Arch. Pharmacal Res. 2014, 37, 821-833).
A mouse model of noise-induced tinnitus has been refined to study the mechanisms that mediate the induction of tinnitus (Li, S.; Choi, V.; Tzounopoulos, T., “Pathogenic plasticity of kv7.2/3 channel activity is essential for the induction of tinnitus.” Proc. Natl. Acad. of Sci. USA 2013, 110, 9980-9985). It is the downregulation of channels Kv7.2/3 that is crucial for the induction of tinnitus. It was found that pharmacological enhancement of Kv7.2/3 with retigabine (also known as ezogabine or Potiga) prevents the development of tinnitus.